Dopamine is a monoamine neurotransmitter found only in the brain, and thus not used anywhere in the somatic nervous system. It is synthesized from L-DOPA by the DOPA Decarboxylase enzyme, which itself is synthesized from tyrosine via Tyrosine Hydroxylase. When it is present intraneuronally (in a neuron but outside of a storage vesicle), Monoamine Oxidase is responsible for breaking it down; hence the danger of using MAOI drugs with dopamine agonists or antagonists. Notably, since the usual route of tyrosine synthesis is from phenylalanine, phenylketoneurics often also have to deal with dopamine deficiency problems along with the rest of their disease. Also, the L-DOPA intermediate is the limiting factor which maintains homeostasis, so when extra L-DOPA is introduced much more dopamine becomes available for use by the brain's dopaminergic neurons.

There are two major, independent pathways which use dopamine in the brain: the nigro-striatal and meso-limbic/meso-cortical. Generally speaking, the nigro-striatal pathway is responsible for consciously controlled motor movement, and the meso-limbic/meso-cortical for reward and goal-related cognition. Concomitant with this difference is the presence of two separate families of dopamine receptors, called the D1 and D2 families respectively. While these were at first thought to be the only two receptors, researchers eventually found D3 and D4 receptors in the D2 family, and a D5 receptor in the D1 family. These each show different affinities for various chemicals, leading to the possibility of drugs with fewer side effects and abuse potentials which work by selecting only one receptor. It is likely that there are more receptors in each family to be found.

The nigra-striatal D1 pathway projects from the Substantia Nigra (near the midbrain) out to the striatum, which has two sub-structures, the caudate and putamen, all of which is cushioned in a brain area called the Basal Ganglia. Since the Basal Ganglia are the pathway from the cortex, probably responsible for consciousness, to the motor system, the nigra-striatal pathway is intimately involved with conscious control of movement.

In Parkinson's disease, dopaminergic neurons in the Substantia Nigra die back badly, leaving little dopamine signal to be received in the striatum. This, in turn, leads to the difficulty of movement which is the classic Parkinsonian symptom. Usually, treatment for Parkinson's begins with administration of L-DOPA, which is converted to dopamine by the remaining neurons and makes neurotransmission to the striatum possible again. This response is so universal that a dose of L-DOPA is considered a good diagnostic tool for Parkinson's -- if the patient doesn't respond, the symptoms are non-Parkinsonian in nature. Notably, all of this dopamine interplay doesn't effect the cerebellum at all, so reflexive physical response is unchanged; even those with advanced Parkinson's disease can sneeze and twitch away from sudden pain.

In direct opposition to the nigra-striatal pathway, the meso-limbic and meso-cortical D2 pathways seem to have nothing to with movement, conscious or otherwise. Instead, it projects from the midbrain, hence the meso- prefix, out to parts of the limbic system and cortex. These are the areas affected by recreational drugs (MPTP, if you can call it recreational, accepted), and also those which are not working properly in schizophrenia.

Specifically, the meso-limbic portion of the projections synapse with the nucleus accumbens, the amygdala, and the hippocampus, and is thought to be responsible for perceptions of pleasure and reward. First, the nucleus accumbens has been referred to as the pleasure center, which pretty much explains its behavior. Rats, when stimulated here by artificially introduced dopamine or, say, an electrical current, will experience a paroxysm of bliss during the stimulus and then seek out whatever caused it in preference to food, water, mating, and so forth. Second, the amygdala is responsible for innate reactions to danger, such as goosebumps and adrenaline release. I couldn't find this in my research, but I'd guess that dopamine stimulation here tells this system not to cause a danger response during a reward condition, even if the cause of the reward was dangerous -- hence distorted reward perception for cutting oneself, etc. Last is the hippocampus, responsible for the formation of long-term memories. Obviously, when reward stimulus dopamine comes in from the midbrain, the exact conditions of the reward are crystallized here in hopes of later seeking out another.

Instead of terminating in the limbic system and being involved with how a reward feels, the meso-cortical pathway projects to the cortex and helps the mind consciously think about the reward. In this way, the pathway is responsible for goal-seeking behavior, where the cortex reasons out a way for the limbic system to achieve the pleasurable reward state. By also being able to reference memories -- see the hippocampal stimulation above -- of how rewards have been obtained in the past, the cortex (specifically the frontal and temporal lobes) can build and execute a plan for achieving another reward.

Before we learned how to purposefully mess with this reward/goal-generation system, it was a perfect balance between the rigidity of reflexive response and the plasticity of learning. That is, we could learn novel conditions for eating, protection from the elements, attraction of the opposite sex, and so forth, but we would always be forced by our pleasure-seeking desire to seek them out again, and not settle for any one over the others. However, sufficiently advanced mammals can find ways of stimulating this system without any actual biological reward like nutrients or reproduction; just as apes seek out fruit fermenting on the ground, junkies seek out dealers with $10 bags.

All solely recreational drugs, by which I mean those besides the pure psychedelics, eventually stimulate the D2 pathway to give the user pleasure. Cocaine does so by blocking the reuptake of synaptic dopamine, leaving it to stimulate the target neuron longer. Amphetamines do so by forcing the neurons' entire reserves of dopamine to be released, creating an abnormally large stimulation. Opiates target opioid receptors, which in turn cause the release of dopamine along the pathway. Even the completely non-dopaminergic and non-addictive MDMA, through serotonin activity, causes cognition which is eventually perceived as pleasurable via the limbic system and its dopamine. None of which would be a big deal, except that the brain is perfectly willing to change itself to maintain homeostasis, and will do so in a bad way when over-pleasured -- see Dopamine, Delta-FosB, and the nature of Addictive Drugs.

Finally, it is rather unclear what role dopamine plays in schizophrenia, but you can be sure that there is one. In schizophrenia, dopamine release throughout the D2 pathway becomes abnormally large. The current best guess is that this plays havoc with the victim's conscious relationships between reward, memory, thought process, and so forth, eventually leading to a break from consensus reality. In any case, the ramp-up of system dopamine at onset is often insidious, which is why schizophrenia can go unnoticed by people close to the victim for a long time, and by the victim through the duration of the illness. Amphetamine psychosis is guessed to work in nearly the same manner, only much more quickly. Schizophrenia, because of its relationship with dopamine, can sometimes be treated with dopamine agonists, which block reception of the excess dopamine; unfortunately, dopamine agonism feels quite abnormal and wrong, leading to the high incidence of schizophrenics going off their medication. Research into controlling dopamine through Anandamide pathways, also targeted by marijuana, is ongoing.

3,4-dihydroxyphenylethylamine

A hormonelike substance with the chemical formula C8H11NO2. It is found in the nervous system as an important neurotransmitter, or substance which transmits nerve signals from neuron to neuron. It is also an intermediate in the productions of the hormones epinephrine (adrenaline) and norepinephrine.


From the BioTech Dictionary at http://biotech.icmb.utexas.edu/. For further information see the BioTech homenode.

Log in or register to write something here or to contact authors.